Discovery of a potent, orally bioavailable pyrimidine VLA-4 antagonist effective in a sheep asthma model

被引：8

作者：

Semko, Christopher M. ^{[1
]}

Chen, Linda ^{[1
]}

Dressen, Darren B. ^{[1
]}

Dreyer, Mark L. ^{[1
]}

Dunn, Whitney ^{[1
]}

Farouz, Francine S. ^{[1
]}

Freedman, Stephen B. ^{[1
]}

Holsztynska, Elizabeth J. ^{[1
]}

Jefferies, Michael ^{[1
]}

Konradi, Andrei W. ^{[1
]}

Liao, Anna ^{[1
]}

Lugar, Judevin ^{[1
]}

Mutter, Linda ^{[1
]}

Pleiss, Michael A. ^{[1
]}

Quinn, Kevin P. ^{[1
]}

Thompson, Thomas ^{[1
]}

Thorsett, Eugene D. ^{[1
]}

Vandevert, Christopher ^{[1
]}

Xu, Ying-Zi ^{[1
]}

Yednock, Ted A. ^{[1
]}

机构：

[1] Elan Pharmaceut Inc, San Francisco, CA 94080 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 06期

关键词：

VLA-4; Integrin; Antagonist; Pyrimidine; INTEGRIN ANTAGONISTS; PHENYLALANINE DERIVATIVES; ALPHA-4; INTEGRIN;

D O I：

10.1016/j.bmcl.2011.01.075

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of N-(pyrimidin-4-yl)-phenylalanine VLA-4 antagonists is described. Optimization of substituents at the 2 and 5 positions of the pyrimidine ring gave 14, a very potent VLA-4 inhibitor which is orally active in a sheep asthma model. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：1741 / 1743

页数：3

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